2-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline → N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-6-methyl-6H-thieno[2,3-b]pyrrole-5-carboxamide

HRID 245731Notes

Reaction equation

HRID 245731 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([B:8]2[O:16][C:13]([CH3:15])([CH3:14])[C:10]([CH3:12])([CH3:11])[O:9]2)=[CH:4][C:3]=1[O:17][CH3:18].C([Mg]Cl)C.[CH3:23][N:24]1[C:28]([C:29](OC)=[O:30])=[CH:27][C:26]2[CH:33]=[CH:34][S:35][C:25]1=2>O1CCCC1.[Cl-].[Na+].O>[CH3:18][O:17][C:3]1[CH:4]=[C:5]([B:8]2[O:9][C:10]([CH3:12])([CH3:11])[C:13]([CH3:14])([CH3:15])[O:16]2)[CH:6]=[CH:7][C:2]=1[NH:1][C:29]([C:28]1[N:24]([CH3:23])[C:25]2[S:35][CH:34]=[CH:33][C:26]=2[CH:27]=1)=[O:30]

Participants

6

Reactant 3

HCID 177502072-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 67364244Methyl 6-methyl-6H-thieno[2,3-b]pyrrole-5-carboxylateHCID 178461633HCID 178461633, compound

Product 1

HCID 67364476N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-6-methyl-6H-thieno[2,3-b]pyrrole-5-carboxamideYield 32.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To 4-amino-3-methoxyphenylboronic acid pinacol ester (1340 mg, 5.38 mmol) in tetrahydrofuran (20 ml) under a nitrogen atmosphere was added slowly a 2M solution of ethylmagnesium chloride in tetrahydrofuran (2.69 ml, 5.38 mmol) and the resulting solution was heated at reflux for one hour. Methyl 6-methyl-6H-thieno[2,3-b]pyrrole-5-carboxylate (500 mg, 2.56 mmol) was added and the reaction mixture was heated at reflux for 18 hours. The reaction mixture was cooled to room temperature and poured in brine. The mixture was extracted three times with ethyl acetate and the combined organic layers were washed subsequently with water and brine. The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (silica gel; heptane with gradient of 0 to 50% of ethyl acetate). The product was dissolved in hot dichloromethane and the remaining solids were removed by filtration. The filtrate was concentrated, the residue dissolved in hot dichloromethane and diethylether was added. The formed solids were collected by filtration, washed with diethylether and dried to yield N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-6-methyl-6H-thieno[2,3-b]pyrrole-5-carboxamide (343 mg).

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureat reflux for one hour
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 18 hours
  5. extractionThe mixture was extracted three times with ethyl acetate
  6. washthe combined organic layers were washed subsequently with water and brine
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (silica gel; heptane with gradient of 0 to 50% of ethyl acetate)
  10. dissolutionThe product was dissolved in hot dichloromethane
  11. customthe remaining solids were removed by filtration
  12. concentrationThe filtrate was concentrated
  13. dissolutionthe residue dissolved in hot dichloromethane
  14. additiondiethylether was added
  15. filtrationThe formed solids were collected by filtration
  16. washwashed with diethylether
  17. customdried

Sources & evidence

ORD record
ord-5eab395bb1d8476abfbe156719e7ce02
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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